Impact of regional SARS-CoV-2 proceedings on changes in diagnoses of pediatric malignancies in Bavaria during the COVID-19 pandemic.

The COVID-19 pandemic affected daily life significantly and had massive consequences for healthcare systems with tremendous regional differences. This retrospective study aimed to investigate whether the pandemic and resulting societal changes impacted the diagnosis of pediatric malignancies in a distinct region. Pediatric cancer cases in Bavaria (2016-2021) and SARS-CoV-2 proceedings during the peak phase of the pandemic (2020-2021) were retrospectively analyzed. All new diagnoses of pediatric malignancies reported from cancer centers in Bavaria were included. Clinical data from pre-pandemic years was compared to diagnoses made during the pandemic. Official SARS-CoV-2 reports were received from the Bavarian Health and Food Safety Authority and data on regional pandemic measures were obtained from the Healthcare Data Platform. With this design, a comprehensive analysis of the pandemic proceedings was performed. We found significantly decreased incidence-rate ratios for pediatric cancer diagnosis during the early spring peak of SARS-CoV-2 as it was observed in May during the pandemic, followed by non-significantly increased metastatic cancer diagnosis two months later. Additionally, the time-to-diagnosis of pediatric malignancies was significantly prolonged during the pandemic, and outpatient contacts were significantly reduced, although the availability of consultations remained the same. From our findings, we may hypothesize that there have been effects on pediatric cancer diagnosis during the COVID-19 pandemic at vulnerable times. Interpretation of changes remains speculative with potential causes from behavior patterns, such as hesitation, concerns, and potential societal changes during phases of public restrictions, rather than overwhelmed medical capacities. Nevertheless, specific awareness is needed to protect this patient population during potential future pandemics.

Isavuconazole therapeutic drug monitoring in critically ill ICU patients: A monocentric retrospective analysis.

BACKGROUND: The broad-spectrum triazole isavuconazole is used for the treatment of invasive aspergillosis and mucormycosis. Data regarding human plasma concentrations in clinical routine of the drug are rare. OBJECTIVES: Plasma concentrations of isavuconazole were determined in critically ill ICU patients while considering different patients' characteristics. METHODS: Retrospective analysis of isavuconazole plasma concentrations were obtained as part of routine therapeutic drug monitoring (TDM) of ICU patients with invasive aspergillosis or other fungal infections treated with isavuconazole. Plasma levels 0-4 h after last dosing were defined as peak levels (Cmax ), those 20-28 h after last dosing as trough levels (Cmin ). RESULTS: Overall, 223 isavuconazole levels of 41 patients were analysed, divided into 141 peak levels and 82 trough levels. The overall median Cmax was 2.36 µg/ml (mean 2.43 µg/ml, range 0.41-7.79 µg/ml) and the overall median Cmin was 1.74 µg/ml (mean 1.77 µg/ml, range 0.24-4.96 µg/ml). In total, 31.7% of the Cmin values of the total cohort were below the plasma target concentrations of 1 µg/ml, defined as EUCAST antifungal clinical breakpoint for Aspergillus fumigatus. Both peak and trough plasma levels of isavuconazole were significantly lower among patients with a body mass index (BMI) ≥25. In addition, a significant correlation was observed between isavuconazole trough levels and sepsis-related organ failure assessment (SOFA) score. CONCLUSIONS: This study shows that isavuconazole plasma concentrations vary in critical ill ICU patients. Significantly lower isavuconazole levels were associated with elevated BMI and higher SOFA score indicating a need of isavuconazole TDM in this specific patient population.

Affinity Series of Genetically Encoded Förster Resonance Energy-Transfer Sensors for Sucrose.

Genetically encoded fluorescent sugar sensors are valuable tools for the discovery of transporters and for quantitative monitoring of sugar steady-state levels in intact tissues. Genetically encoded Förster resonance energy-transfer sensors for glucose have been designed and optimized extensively, and a full series of affinity mutants is available for in vivo studies. However, to date, only a single improved sucrose sensor FLIPsuc-90µΔ1 with Km for sucrose of ∼90 µM was available. This sucrose sensor was engineered on the basis of an Agrobacterium tumefaciens sugar-binding protein. Here, we took a two-step approach to first improve the dynamic range of the FLIPsuc sensor and then expand the detection range from micro- to millimolar sucrose concentrations by mutating a key residue in the binding site. The resulting series of sucrose sensors may enable investigation of sucrose transporter candidates and comprehensive in vivo analyses of sucrose concentration in plants. Since FLIPsuc-90µ also detects trehalose in animal cells, the new series of sensors will likely be suitable for investigating trehalose transport and monitor trehalose steady-state levels in vivo.